The role of immunity in protection from mucosal SIV infection in macaques

The need for an effective vaccine against HIV has prompted a refocusing of attention on mucosal immunity. More than 75% of all infections are acquired across a mucosal surface. It is therefore a prerequisite for a vaccine to target directly the mucosal tissues or indirectly the regional lymph nodes in order to prevent or control viral replication. Although mucosal immunization has induced responses at the genital or rectal surfaces, immune mechanisms alone have not been shown to be sufficient to contain infections in macaques. A growing body of evidence suggests that a dual mechanism may be required for effective mucosal protection, mediated by specific CD4 and CD8 T cell and antibody responses to the immunizing agents, plus innate antiviral factors and beta chemokines that down-regulate CCR5 coreceptors. Targeted iliac lymph node immunization with SIV gp120 and p27 in alum prevents SIV infection or significantly decreases the viral load when immunized macaques were challenged with SIV by the rectal route. Indeed, in addition to specific immunity, including significant SIgA antibody secreting cells in the iliac lymph nodes, CD8-suppressor factor and the 3beta chemokines (RANTES, MIP-1alpha and MIP-1beta) are significantly associated with protection against rectal mucosal SIV infection.